The proposed work is intended to elucidate aspects of how proteins and lipids interact. Several distinct projects are being carried out simultaneously, with each emphasizing a different facet of the problem. Most of our effort is directed towards learning in detail how the membrane enzyme pyruvate oxidase binds to phospholipids and detergents, and furthermore to analyze the effect of the lipid binding on both the enzyme structure and function. We have shown qualitatively that the binding of the enzyme to the membrane is controlled by the amount of substrate, pyruvate, which is present. The next stage will be to quantitate the changes in this binding, and to isolate the portions of the enzyme responsible for the membrane affinity. A second project is the study of changes in the E. coli envelope which accompany alterations in the bioenergetic pathways in the organism. The indicated alterations are large in magnitude and of unknown origin. Finally, the specific 1:1 peptide-lipid complex which forms between the antibiotic bacitracin and farnesyl pyrophosphate in the presence of a divalent cation is being studied as a model protein-lipid interaction.